PlumX Metrics
Embed PlumX Metrics

Microfluidic study of retention and elimination of abnormal red blood cells by human spleen with implications for sickle cell disease

Proceedings of the National Academy of Sciences of the United States of America, ISSN: 1091-6490, Vol: 120, Issue: 6, Page: e2217607120
2023
  • 16
    Citations
  • 0
    Usage
  • 40
    Captures
  • 3
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    16
    • Citation Indexes
      16
  • Captures
    40
  • Mentions
    3
    • News Mentions
      3
      • 3

Most Recent News

News “Spleen-on-a-Chip” Provides Insights Into Sickle Cell Disease Researchers at MIT, Nanyang Technological University in Singapore, the Pasteur Institute in Paris, and other institutions have now designed a microfluidic device, or “spleen-on-a-chip,” th

Every day, billions of red blood cells pass through the spleen, an organ that is responsible for filtering out old or damaged blood cells. This

Article Description

The spleen clears altered red blood cells (RBCs) from circulation, contributing to the balance between RBC formation (erythropoiesis) and removal. The splenic RBC retention and elimination occur predominantly in open circulation where RBCs flow through macrophages and inter-endothelial slits (IESs). The mechanisms underlying and interconnecting these processes significantly impact clinical outcomes. In sickle cell disease (SCD), blockage of intrasplenic sickled RBCs is observed in infants splenectomized due to acute splenic sequestration crisis (ASSC). This life-threatening RBC pooling and organ swelling event is plausibly triggered or enhanced by intra-tissular hypoxia. We present an oxygen-mediated spleen-on-a-chip platform for in vitro investigations of the homeostatic balance in the spleen. To demonstrate and validate the benefits of this general microfluidic platform, we focus on SCD and study the effects of hypoxia on splenic RBC retention and elimination. We observe that RBC retention by IESs and RBC–macrophage adhesion are faster in blood samples from SCD patients than those from healthy subjects. This difference is markedly exacerbated under hypoxia. Moreover, the sickled RBCs under hypoxia show distinctly different phagocytosis processes from those non-sickled RBCs under hypoxia or normoxia. We find that reoxygenation significantly alleviates RBC retention at IESs, and leads to rapid unsickling and fragmentation of the ingested sickled RBCs inside macrophages. These results provide unique mechanistic insights into how the spleen maintains its homeostatic balance between splenic RBC retention and elimination, and shed light on how disruptions in this balance could lead to anemia, splenomegaly, and ASSC in SCD and possible clinical manifestations in other hematologic diseases.

Bibliographic Details

Qiang, Yuhao; Sissoko, Abdoulaye; Liu, Zixiang L; Dong, Ting; Zheng, Fuyin; Kong, Fang; Higgins, John M; Karniadakis, George E; Buffet, Pierre A; Suresh, Subra; Dao, Ming

Proceedings of the National Academy of Sciences

Multidisciplinary

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know